Evaluation of the clinical effects of atropine in combination with remifentanil in children undergoing surgery for acute appendicitis.

BACKGROUND: Acute appendicitis (AA) is the most common cause of acute abdomen in children. Anesthesia significantly influences the surgical treatment of AA in children, making the scientific and effective selection of anesthetics crucial. AIM: To assess the clinical effect of atropine (ATR) in combination with remifentanil (REMI) in children undergoing surgery for AA. METHODS: In total, 108 cases of pediatric AA treated between May 2020 and May 2023 were selected, 58 of which received ATR + REMI [research group (RG)] and 50 who received REMI [control group (CG)]. Comparative analyses were conducted on the time to loss of eyelash reflex, pain resolution time, recovery time from anesthesia, incidence of adverse events (AEs; respiratory depression, hypoxemia, bradycardia, nausea and vomiting, and hypotension), intraoperative responses (head shaking, limb activity, orientation recovery, safe departure time from the operating room), hemodynamic parameters [oxygen saturation (SPO2), mean arterial pressure, heart rate, and respiratory rate], postoperative sedation score (Ramsay score), and pain level [the Face, Legs, Activity, Cry, Consolability (FLACC) Behavioral Scale]. RESULTS: Compared with the CG, the RG showed significantly shorter time to loss of eyelash reflex, pain resolution, recovery from anesthesia, and safe departure from the operating room. Furthermore, the incidence rates of overall AEs (head shaking, limb activity, etc.) were lower, and influences on intraoperative hemodynamic parameters and stress response indexes were fewer. The Ramsay score at 30 min after extubation and the FLACC score at 60 min after extubation were significantly lower in the RG than in the CG. CONCLUSION: ATR + REMI is superior to REMI alone in children undergoing AA surgery, with a lower incidence of AEs, fewer influences on hemodynamics and stress responses, and better post-anesthesia recovery.

The corrosion behavior of carbon steel under coexistence of carbon dioxide and SRB.

The corrosion behavior of carbon steel under the coexistence of carbon dioxide and SRB was studied by means of corrosion weight loss, SEM, EDS, in situ pH test, and other methods. The results showed that Chloride ions, temperature, pH, and oxygen coexist with iron bacteria will affect the corrosion under the coexistence of CO2 and SRB, and SRB tends to grow in a favorable environment for itself, and the corrosion rate of X52N at 42 days is slightly higher than that at 21 days. However, the pitting depth increased sharply from 21.20 µm in 21 days to 39.79 µm in 42 days. So that the corrosion can be divided into two stages. First, SRB catalyze the dissolution of FeCO3, leading to local uniform corrosion. Second, SRB directly obtain electrons from the metal surface, resulting in local pitting. In addition, the environment under the stable mineralized biofilm was found to be slightly alkaline.

Multi-cohort validation: A comprehensive exploration of prognostic marker in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common form of RCC. It is characterized by resistance to traditional radiotherapy and chemotherapy, as well as an unfavorable clinical prognosis. Although TYMP is implicated in the advancement of tumor progression, the role of TYMP in ccRCC is still not understood. Heightened TYMP expression was identified in ccRCC through database mining and confirmed in RCC cell lines. Indeed, TYMP knockdown impacted RCC cell proliferation, migration, and invasion in vitro. TYMP showed a positive correlation with clinicopathological parameters (histological grade, pathological stage). Moreover, patients with high TYMP expression were indicative of poor prognosis in TCGA-ccRCC and external cohorts. The results of single-cell analysis showed that the distribution of TYMP was predominantly observed in monocytes and macrophages. Furthermore, there is a significant association between TYMP and immune status. Methylation analysis further elucidated the relationship between TYMP expression and multiple methylation sites. Drug sensitivity analysis unveiled potential pharmaceutical options. Additionally, mutation analyses identified an association between TYMP and the ccRCC driver genes like BAP1 and ROS1. In summary, TYMP may serve as a reliable prognostic indicator for ccRCC.

LncRNA-SNHG5 mediates activation of hepatic stellate cells by regulating NF2 and Hippo pathway.

Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is an oncogene found in various human cancers. However, it is unclear what role SNHG5 plays in activating hepatic stellate cells (HSCs) and liver fibrosis. In this study, SNHG5 was found to be upregulated in activated HSCs in vitro and in primary HSCs isolated from fibrotic liver in vivo, and inhibition of SNHG5 suppressed HSC activation. Notably, Neurofibromin 2 (NF2), the main activator for Hippo signalling, was involved in the effects of SNHG5 on HSC activation. The interaction between SNHG5 and NF2 protein was further confirmed, and preventing the combination of the two could effectively block the effects of SNHG5 inhibition on EMT process and Hippo signaling. Additionally, higher SNHG5 was found in chronic hepatitis B patients and associated with the fibrosis stage. Altogether, we demonstrate that SNHG5 could serve as an activated HSCs regulator via regulating NF2 and Hippo pathway.

Circular RNA cVIM promotes hepatic stellate cell activation in liver fibrosis via miR-122-5p/miR-9-5p-mediated TGF-ß signaling cascade.

Hepatic stellate cell (HSC) activation is considered as a central driver of liver fibrosis and effective suppression of HSC activation contributes to the treatment of liver fibrosis. Circular RNAs (circRNAs) have been reported to be important in tumor progression. However, the contributions of circRNAs in liver fibrosis remain largely unclear. The liver fibrosis-specific circRNA was explored by a circRNA microarray and cVIM (a circRNA derived from exons 4 to 8 of the vimentin gene mmu_circ_32994) was selected as the research object. Further studies revealed that cVIM, mainly expressed in the cytoplasm, may act as a sponge for miR-122-5p and miR-9-5p to enhance expression of type I TGF-ß receptor (TGFBR1) and TGFBR2 and promotes activation of the TGF-ß/Smad pathway, thereby accelerating the progression of liver fibrosis. Our results demonstrate a vital role for cVIM in promoting liver fibrosis progression and provide a fresh perspective on circRNAs in liver fibrosis.

Association between emergence delirium and brain status parameters in children undergoing general anesthesia: A prospective observational study.

INTRODUCTION: Emergence delirium is a common postoperative neurological complication in children after general anesthesia. There is no valid tool to predict emergence delirium. Wavelet index, pain threshold index, anxiety index, and comfort index are real-time brain status parameters extracted from the electroencephalogram, which have recently been developed. The aim is to evaluate the association between real-time brain status parameters during emergence and emergence delirium in children undergoing general anesthesia. METHODS: One hundred and thirty patients between 3 and 6 years of age undergoing dental surgery under general anesthesia were enrolled in the study. Real-time electroencephalogram data were recorded at four different time points from end of anesthetics administration (T1), end of surgery (T2), extubation (T3), and response (eye opening, movement) to verbal stimulation (T4). Each patient was assessed for emergence delirium using the Pediatric Anesthesia Emergence Delirium scale. Receiver operating characteristics curves and the associated areas under the curves were computed to analyze the ability of wavelet index, pain threshold index, anxiety index, and comfort index to predict emergence delirium. RESULTS: One hundred and sixteen patients were included for final analysis. During recovery from general anesthesia, brain status parameters increased significantly from T1 (wavelet index, 59.5 ± 6.2; pain threshold index, 61.7 ± 5.3; anxiety index, 9.2 ± 2.5; comfort index, 21.6 ± 8.7) to T4 (wavelet index, 67.4 ± 9.4; pain threshold index, 73.2 ± 9.1; anxiety index, 38.6 ± 11.2; comfort index, 66.1 ± 16.5; p < .001). To predict emergence delirium, areas under the curves [95% CI] for anxiety index were 0.84 [0.75-0.93] (p < .001), and comfort index was 0.89 [0.81-0.96] (p < .001). The Pediatric Anesthesia Emergence Delirium scale scores of 37 patients were higher than 10 indicating emergence delirium, and the incidence of emergence delirium was 31.90%. The sensitivity and specificity of anxiety index with corresponding cutoff values in predicting emergence delirium were 73.0% and 89.9%, and the sensitivity and specificity of comfort index in predicting emergence delirium were 91.9% and 83.5%. The best cutoff values for anxiety index and comfort index to predict emergence delirium were 46.5 and 68.5, respectively. The areas under the curves [95% CI] of wavelet index to predict emergence delirium were 0.43 [0.31-0.35] (p = .27), while the areas under the curves [95% CI] of pain threshold index to predict emergence delirium were 0.49 [0.37-0.62] (p = .73). DISCUSSION: Both anxiety index and comfort index derived from electroencephalogram wavelet analysis were associated with emergence delirium in pediatric patients undergoing general anesthesia for dental surgery. Wavelet index and pain threshold index were not associated with emergence delirium during general anesthesia for dental surgery in children. CONCLUSIONS: AnXi and CFi might be used to guide anesthesiologists to identify and intervene ED in children.

Comparison between the modified Blalock-Taussig shunt and right ventricular outflow tract stent in the palliative treatment for tetralogy of Fallot. / 改良Blalock-Taussigåˆ†æµæœ¯ä¸Žå³å¿ƒå®¤æµå‡ºé“æ”¯æž¶æ¤å ¥æœ¯å§‘æ¯æ€§æ²»ç–—æ³•æ´›å››è”ç—‡çš„æ¯”è¾ƒ.

OBJECTIVES: For patients with tetralogy of Fallot (TOF) who are not suitable candidates for primary corrective surgery or have a high surgical risk, transcatheter right ventricular outflow tract (RVOT) stent implantation is considered a safe and effective palliative intervention. This study aims to investigate the therapeutic outcomes of RVOT stent implantation in neonates and infants with TOF in comparison with the modified Blalock-Taussig shunt (mBTS) and to compare the impact of the 2 palliative interventions on arterial oxygen saturation and pulmonary artery development in pediatric patients. METHODS: Clinical data of 32 patients with TOF admitted to the Second Xiangya Hospital of Central South University from March 2011 to March 2021 were retrospectively collected. The patients were divided into an mBTS group (undergoing mBTS, n=15) and a stent implantation group (undergoing RVOT stenting, n=17) according to the surgical procedures. The 2 groups were assessed and compared in the surgical-related arterial oxygen saturation, postoperative complication rate, mortality rate, and re-intervention rate. The development of the patients' main pulmonary artery, right pulmonary artery, and left pulmonary artery was assessed by z-scores according to echocardiographic results. RESULTS: The children in the stent implantation group were younger and less weighed compared with the mBTS group (both P<0.05). Compared with the preoperative period, children in the stent implantation group had significantly higher arterial oxygen saturation [(75±17)% vs (96±3)%, P=0.026]; z-scores of pulmonary trunk [(-2.82±1.27) points vs (0.86±0.77) points, P=0.014], right pulmonary artery [(-1.88±0.59) points vs (-0.28±0.71) points, P=0.011], and left pulmonary artery [(-2.34±0.36) points vs (-1.67±0.36) points, P=0.036] were significantly increased. However, there were no significant differences in arterial oxygen saturation and pulmonary artery z-scores between pre- and post-mBTS procedures (all P>0.05). CONCLUSIONS: RVOT stent would have good surgical outcomes used in TOF patients with low weight and severe comorbidities. It also leads to an higher postoperative oxygen saturation and better promotion of pulmonary artery growth with RVOT stent compared to mBTS.

Identification and validation of a prognostic risk-scoring model based on sphingolipid metabolism-associated cluster in colon adenocarcinoma.

Colon adenocarcinoma (COAD) is the primary factor responsible for cancer-related mortalities in western countries, and its development and progression are affected by altered sphingolipid metabolism. The current study aimed at investigating the effects of sphingolipid metabolism-related (SLP) genes on multiple human cancers, especially on COAD. We obtained 1287 SLP genes from the GeneCard and MsigDb databases along with the public transcriptome data and the related clinical information. The univariate Cox regression analysis suggested that 26 SLP genes were substantially related to the prognosis of COAD, and a majority of SLP genes served as the risk genes for the tumor, insinuating a potential pathogenic effect of SLP in COAD development. Pan-cancer characterization of SLP genes summarized their expression traits, mutation traits, and methylation levels. Subsequently, we focused on the thorough research of COAD. With the help of unsupervised clustering, 1008 COAD patients were successfully divided into two distinct subtypes (C1 and C2). C1 subtype is characterized by a poor prognosis, activation of SLP pathways, high expression of SLP genes, disordered carcinogenic pathways, and immune microenvironment. Based on the clusters of SLP, we developed and validated a novel prognostic model, consisting of ANO1, C2CD4A, EEF1A2, GRP, HEYL, IGF1, LAMA2, LSAMP, RBP1, and TCEAL2, to quantitatively evaluate the clinical outcomes of COAD. The Kaplain-Meier survival curves and ROC curves highlighted the accuracy of our SLP model in both internal and external cohorts. Compared to normal colon tissues, expression of C2CD4A was detected to be significantly higher in COAD; whereas, expression levels of EEF1A2, IGF1, and TCEAL2 were detected to be significantly lower in COAD. Overall, our research emphasized the pathogenic role of SLP in COAD and found that targeting SLP might help improve the clinical outcomes of COAD. The risk model based on SLP metabolism provided a new horizon for prognosis assessment and customized patient intervention.

GPS-Uber: a hybrid-learning framework for prediction of general and E3-specific lysine ubiquitination sites.

As an important post-translational modification, lysine ubiquitination participates in numerous biological processes and is involved in human diseases, whereas the site specificity of ubiquitination is mainly decided by ubiquitin-protein ligases (E3s). Although numerous ubiquitination predictors have been developed, computational prediction of E3-specific ubiquitination sites is still a great challenge. Here, we carefully reviewed the existing tools for the prediction of general ubiquitination sites. Also, we developed a tool named GPS-Uber for the prediction of general and E3-specific ubiquitination sites. From the literature, we manually collected 1311 experimentally identified site-specific E3-substrate relations, which were classified into different clusters based on corresponding E3s at different levels. To predict general ubiquitination sites, we integrated 10 types of sequence and structure features, as well as three types of algorithms including penalized logistic regression, deep neural network and convolutional neural network. Compared with other existing tools, the general model in GPS-Uber exhibited a highly competitive accuracy, with an area under curve values of 0.7649. Then, transfer learning was adopted for each E3 cluster to construct E3-specific models, and in total 112 individual E3-specific predictors were implemented. Using GPS-Uber, we conducted a systematic prediction of human cancer-associated ubiquitination events, which could be helpful for further experimental consideration. GPS-Uber will be regularly updated, and its online service is free for academic research at http://gpsuber.biocuckoo.cn/.

iCAL: a new pipeline to investigate autophagy selectivity and cancer.

Macroautophagy/autophagy can selectively degrade misfolded proteins, damaged organelles and other cargoes. It is conceivable that alteration of the degradation processes could disrupt normal cellular signaling and contribute to human diseases such as cancer. To explore the link between aberrant autophagy selectivity and human cancer, we have developed a pipeline called "inference of cancer-associated LC3-interacting region-containing proteins" (iCAL), which integrates a sequence-based predictor, a model-based computational method, publicly available cancer mutations, and multiple experimental approaches. Using iCAL, we have identified 222 LIR motif-associated mutations (LAMs) in 148 LIR-containing proteins (LIRCPs), and validated that LAMs in ATG4B, STBD1, EHMT2 and BRAF impair their interactions with LC3 and/or autophagy activities. Moreover, we uncovered that STBD1, a previously poorly-characterized protein, inhibits tumor growth via metabolism reprogramming in cancer cells. A patient-derived mutation in STBD1 (W203C) disrupts the interaction with LC3 and promotes tumor growth. Taken together, iCAL provides an exciting new avenue to discover novel autophagy pathways that contribute to carcinogenesis.

Model-based analysis uncovers mutations altering autophagy selectivity in human cancer.

Autophagy can selectively target protein aggregates, pathogens, and dysfunctional organelles for the lysosomal degradation. Aberrant regulation of autophagy promotes tumorigenesis, while it is far less clear whether and how tumor-specific alterations result in autophagic aberrance. To form a link between aberrant autophagy selectivity and human cancer, we establish a computational pipeline and prioritize 222 potential LIR (LC3-interacting region) motif-associated mutations (LAMs) in 148 proteins. We validate LAMs in multiple proteins including ATG4B, STBD1, EHMT2 and BRAF that impair their interactions with LC3 and autophagy activities. Using a combination of transcriptomic, metabolomic and additional experimental assays, we show that STBD1, a poorly-characterized protein, inhibits tumor growth via modulating glycogen autophagy, while a patient-derived W203C mutation on LIR abolishes its cancer inhibitory function. This work suggests that altered autophagy selectivity is a frequently-used mechanism by cancer cells to survive during various stresses, and provides a framework to discover additional autophagy-related pathways that influence carcinogenesis.

Pentoxifylline for the prevention of contrast-induced nephropathy: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To summarise current evidence on the use of pentoxifylline (PTX) to prevent contrast-induced nephropathy (CIN). METHODS: The PubMed, Embase and CENTRAL databases were searched for randomised controlled trials including patients with and without PTX undergoing contrast media exposure. We analysed the incidence of CIN and serum creatinine changes before and after contrast media exposure. All statistical analyses were conducted with Review Manager V.5.3. RESULTS: We finally enrolled in seven randomised controlled trials with a total of 1484 patients in this analysis. All of seven included studies were performed in patients undergoing angioplasty or stenting. The overall rates of CIN were 8.8% and 10.4% in the PTX groups and control groups, respectively. However, no significant reduction in the CIN rate was observed in the patients treated with PTX compared with the control groups (OR 0.81, 95% CI 0.57 to 1.13, I2=0, p=0.21). All studies reported no hospital mortality and the new requirement for dialysis during the trials. CONCLUSION: Perioperative administration of PTX to patients undergoing angioplasty did not significantly reduce the development of CIN but showed some weak tendency of lower serum creatinine increase. Based on the available trials, the evidence does not support the administration of PTX for the prevention of CIN. More trials with larger sample sizes are needed to evaluate the role of PTX in CIN prevention.

GPS-Palm: a deep learning-based graphic presentation system for the prediction of S-palmitoylation sites in proteins.

As an important reversible lipid modification, S-palmitoylation mainly occurs at specific cysteine residues in proteins, participates in regulating various biological processes and is associated with human diseases. Besides experimental assays, computational prediction of S-palmitoylation sites can efficiently generate helpful candidates for further experimental consideration. Here, we reviewed the current progress in the development of S-palmitoylation site predictors, as well as training data sets, informative features and algorithms used in these tools. Then, we compiled a benchmark data set containing 3098 known S-palmitoylation sites identified from small- or large-scale experiments, and developed a new method named data quality discrimination (DQD) to distinguish data quality weights (DQWs) between the two types of the sites. Besides DQD and our previous methods, we encoded sequence similarity values into images, constructed a deep learning framework of convolutional neural networks (CNNs) and developed a novel algorithm of graphic presentation system (GPS) 6.0. We further integrated nine additional types of sequence-based and structural features, implemented parallel CNNs (pCNNs) and designed a new predictor called GPS-Palm. Compared with other existing tools, GPS-Palm showed a >31.3% improvement of the area under the curve (AUC) value (0.855 versus 0.651) for general prediction of S-palmitoylation sites. We also produced two species-specific predictors, with corresponding AUC values of 0.900 and 0.897 for predicting human- and mouse-specific sites, respectively. GPS-Palm is free for academic research at http://gpspalm.biocuckoo.cn/.

HIF-1a regulates hypoxia-induced autophagy via translocation of ANKRD37 in colon cancer.

Autophagy is a basic catabolic response that eukaryotic cells use to degrade unnecessary or dysfunctional cellular components in an orderly and regulated manner. It plays important roles in maintaining cellular homeostasis, energy homeostasis, response to environmental stimuli, and the development of cancer. In solid tumors, hypoxia induces an increased HIF-1a that activates autophagy. However, the exact mechanism by which induced HIF-1a stimulates autophagy in cancer cells remains elusive. In the present study, we confirmed that ANKRD37 is upregulated in colon cancer tissue. Moreover, the higher expression level of ANKRD37 is related to a poorer survival rate. Using RNA interference, immunoblot, and immunofluorescence, we discovered that in cancer cell line RKO, hypoxia-induced HIF-1a regulates autophagy activity by increasing ANKRD37 level. In addition, intranuclear ANKRD37 played an important role in the regulation of hypoxia-induced autophagy. The translocation of ANKRD37 into cell nuclear is required for promoting cell growth and HIF-1a induced autophagy. These findings provide new insights to understand the hypoxia regulation mechanisms and the role of autophagy in cancer development.

[Regulatory effect of Di'ao Xinxuekang on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats].

The aim of this paper was to observe the effect of Di'ao Xinxuekang(DXXK) on TLR4/MyD88/NF-κB signaling pathway in atherosclerotic rats, and to explore its anti-atherosclerotic mechanism. Sixty SD rats were randomly divided into normal group, model group, atorvastatin group(4.0 mg·kg~(-1)), and DXXK groups(100, 30, 10 mg·kg~(-1)), with 10 rats in each group. The atherosclerosis model was induced by high fat diet plus vitamin D_2. Experimental drugs were administered intragastrically once daily for 8 weeks starting from the 9 th week. Biochemical analyzers were used to detect levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) in blood lipid. The levels of serum tumor necrosis factor(TNF)-α, interleukin(IL)-6 and IL-1ß were detected by ELISA. Pathological changes of aortic tissues were observed by using Sudan Ⅳ and HE staining. The mRNA and protein expressions of TLR4, MyD88 and NF-κB p65 in aortic tissues were detected by RT-PCR and Western blot, respectively. As compared with the model group, TC, TG, and LDL-C levels in serum were significantly decreased, HDL-C content was significantly increased, and levels of TNF-α, IL-6, and IL-1ß in serum were significantly decreased in atorvastatin group and DXXK high and middle dose groups. Aortic lesions in atorvastatin group and DXXK group were significantly improved, and the mRNA and protein expressions of TLR4, MyD88, NF-κB p65 in the aorta were decreased. DXXK has a preventive and therapeutic effect on atherosclerosis in rats, and its mechanism may be related to inhibiting inflammatory reaction by regulating TLR4/MyD88/NF-κB signal transduction, thereby inhibiting the progression of atherosclerosis.

Effects of relative low minute ventilation on cerebral haemodynamics in infants undergoing ventricular septal defect repair.

BACKGROUND: Ventilation-associated changes in blood carbon dioxide levels are associated with various physiological changes in infants undergoing surgery. Studies on the effects of mechanical ventilation on cerebral haemodynamics especially for infants with CHD are scarce. AIM: This study was done to compare the changes in regional cerebral oxygen saturation and cerebral blood flow velocity when the end-tidal carbon dioxide partial pressure changed during different minute ventilation settings in infants undergoing ventricular septal defect repair. METHODS: A total of 67 patients less than 1 year old with ventricular septal defect were enrolled, and 65 patients (age: 6.7 ± 3.4 months, weight: 6.4 ± 1.5 kg) were studied. After anaesthesia induction and endotracheal intubation, the same mechanical ventilation mode (The fraction of inspired oxygen was 50%, and the inspiratory-to-expiratory ratio was 1:1.5.) was adopted. The end-tidal carbon dioxide partial pressure of 30 mmHg (T1), 35 mmHg (T2), 40 mmHg (T3), or 45 mmHg (T4) were obtained, respectively, by adjusting tidal volume and respiratory rate. Minute ventilation per kilogram was calculated by the formula: minute ventilation per kilogram = tidal volume * respiratory rate/kg. Regional cerebral oxygen saturation was monitored by real-time near-infrared spectroscopy. Cerebral blood flow velocity (systolic flow velocity, end-diastolic flow velocity, and mean flow velocity), pulsatility index, and resistance index were measured intermittently by transcranial Doppler. Systolic pressure, diastolic pressure, stroke volume index, and cardiac index were recorded using the pressure recording analytical method. RESULTS: As the end-tidal carbon dioxide partial pressure increased from 30 to 45 mmHg, regional cerebral oxygen saturation increased significantly from 69 ± 5% to 79 ± 4% (p < 0.001). Cerebral blood flow velocity (systolic flow velocity, end-diastolic flow velocity, and mean flow velocity) increased linearly, while pulsatility index and resistance index decreased linearly from T1 (systolic flow velocity, 84 ± 19 cm/second; end-diastolic flow velocity, 14 ± 4 cm/second; mean flow velocity, 36 ± 10 cm/second; pulsatility index, 2.13 ± 0.59; resistance index, 0.84 ± 0.12) to T4 (systolic flow velocity, 113 ± 22 cm/second; end-diastolic flow velocity, 31 ± 6 cm/second; mean flow velocity, 58 ± 11 cm/second; pulsatility index, 1.44 ± 0.34; resistance index, 0.72 ± 0.07) (p < 0.001). There were significant differences in changes of systolic flow velocity, end-diastolic flow velocity, mean flow velocity, pulsatility index, and resistance index as the end-tidal carbon dioxide partial pressure increased from 30 to 45 mmHg between subgroups of infants ≤6 and infants >6 months, while the changes of regional cerebral oxygen saturation between subgroups were not statistically different. Regional cerebral oxygen saturation and cerebral blood flow velocity (systolic flow velocity, end-diastolic flow velocity, and mean flow velocity) were negatively correlated with minute ventilation per kilogram (r = -0.538, r = -0.379, r = -0.504, r = -0.505, p < 0.001). Pulsatility index and resistance index were positively related to minute ventilation per kilogram (r = 0.464, r = 0.439, p < 0.001). The diastolic pressure was significantly reduced from T1 (41 ± 7 mmHg) to T4 (37 ± 6 mmHg) (p < 0.001). There were no significant differences in systolic pressure, stroke volume index, and cardiac index with the change of end-tidal carbon dioxide partial pressure from T1 to T4 (p = 0.063, p = 0.382, p = 0.165, p > 0.05). CONCLUSION: A relative low minute ventilation strategy increases regional cerebral oxygen saturation and cerebral blood flow, which may improve cerebral oxygenation and brain perfusion in infants undergoing ventricular septal defect repair.

DrLLPS: a data resource of liquid-liquid phase separation in eukaryotes.

Here, we presented an integrative database named DrLLPS (http://llps.biocuckoo.cn/) for proteins involved in liquid-liquid phase separation (LLPS), which is a ubiquitous and crucial mechanism for spatiotemporal organization of various biochemical reactions, by creating membraneless organelles (MLOs) in eukaryotic cells. From the literature, we manually collected 150 scaffold proteins that are drivers of LLPS, 987 regulators that contribute in modulating LLPS, and 8148 potential client proteins that might be dispensable for the formation of MLOs, which were then categorized into 40 biomolecular condensates. We searched potential orthologs of these known proteins, and in total DrLLPS contained 437 887 known and potential LLPS-associated proteins in 164 eukaryotes. Furthermore, we carefully annotated LLPS-associated proteins in eight model organisms, by using the knowledge integrated from 110 widely used resources that covered 16 aspects, including protein disordered regions, domain annotations, post-translational modifications (PTMs), genetic variations, cancer mutations, molecular interactions, disease-associated information, drug-target relations, physicochemical property, protein functional annotations, protein expressions/proteomics, protein 3D structures, subcellular localizations, mRNA expressions, DNA & RNA elements, and DNA methylations. We anticipate DrLLPS can serve as a helpful resource for further analysis of LLPS.

Echocardiography-guided percutaneous closure of patent ductus arteriosus without arterial access: Feasibility and safety for a new strategy.

OBJECTIVE: To evaluate the feasibility and safety of device closure of patent ductus arteriosus (PDA) using only venous access under echocardiography guidance alone.
 Methods: A total of 102 consecutive pediatric patients underwent transcatheter PDA closure without arterial access, under the guidance of only echocardiography. The patients were followed up by clinical examination, electrocardiogram, and echocardiogram at 1, 3, 6 12, and 24 months.
 Results: Transvenous PDA closure under echocardiographic guidance was successful in 99 (97.1%) patients. There were no acute procedural complications or severe adverse events. The duration ranged from 10 to 65 minutes (median, 21 minutes). Immediate complete closure of PDA was achieved in 87 patients (87.9%), and 100% of the patients were completely closed after 24 h. There were no severe adverse events in the period of 1-24 months (median, 12 months) follow up.
 Conclusion: Transvenous PDA closure without fluoroscopy avoids radiation exposure, contrast agent usage and potential arterial complications. It can be used as an alternative procedure, especially for children.

miR-195 inhibited abnormal activation of osteoblast differentiation in MC3T3-E1 cells via targeting RAF-1.

BACKGROUND: Recent reports have demonstrated that RAF-1L613V (a mutant of RAF-1) mutant mice show bone deformities similar to Noonan syndrome. It has been suggested that RAF-1L613V might abnormally activate osteoblast differentiation of MC3T3-E1 cells. METHODS: To demonstrate that RAF-1 is associated with bone deformity and that RAF-1L613V dependent bone deformity could be inhibited by microRNA-195 (miR-195), we first investigated the amplifying influence of wild-type RAF-1 (WT) or RAF-1L613V (L613V) on the viability and differentiation of MC3T3-E1 cells induced by bone morphogenetic protein-2 (BMP-2) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. Subsequently, we investigated the blocking effect and its mechanism of miR-195 for abnormal activation of osteoblast differentiation of MC3T3-E1 cells via targeting RAF-1. RESULTS: RAF-1, especially RAF-1L613V, abnormally activates osteoblast differentiation of MC3T3-E1 cells induced by BMP-2. Meanwhile, miR-195 could inhibit the cell viability and differentiation of MC3T3-E1 cells. Transfection of miR-195 largely suppressed the L613V-induced viability and osteoblast differentiation of MC3T3-E1 cells and attenuated the accelerative effect of L613V on runt-related transcription factor-2 (Runx2), Osterix (OSX), alkaline phosphatase (ALP), osteocalcin (OCN), and distal-less homeobox 5 (DLX5) osteogenic gene expressions. In addition, miR-195 decreased the expression of RAF-1 mRNA and protein by directly targeting the 3'-untranslated regions (3'-UTR) of RAF-1 mRNA in MC3T3-E1 cells. CONCLUSIONS: Our findings indicated that miR-195 inhibited WT and L613V RAF-1 induced hyperactive osteoblast differentiation in MC3T3-E1 cells by targeting RAF-1. miR-195 might be a novel therapeutic agent for the treatment of L613V-induced bone deformity in Noonan syndrome.

Transapical transcatheter device closure of relapse left ventricular diverticulum: a novel minimally invasive technique for reoperation.

We describe a novel minimally invasive technique, transapical transcatheter device closure of relapse left ventricular diverticulum (LVD) under transesophageal echocardiography (TEE) guidance. The patient previously underwent LVD primary repair and mitral valvular replacement. The anatomical characteristics of the relapse LVD and its adjacent structures are detailedly delineated by echocardiography. The relapse LVD is then managed by transapical transcatheter device closure under TEE guidance. This novel minimally invasive technique is not only limited in relapse LVD, but also could be extensively applied in other cardiac reoperation, such as perivalvular leak closure after valvular replacement.